MRP proteins as potential mediators of heavy metal resistance in zebrafish cells

MRP proteins as potential mediators of heavy metal resistance in zebrafish cells
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MRP 蛋白作为斑马鱼细胞重金属抗性的潜在介质

DOI:
10.1016/j.cbpc.2010.12.001
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发表时间:
2011-04-01
影响因子:
3.9
通讯作者:
Cui, Zongbin
Cui, Zongbin
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Long, Yong;Li, Qing;Cui, Zongbin

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Acquired resistance of mammalian cells to heavy metals is closely relevant to enhanced expression of several multidrug resistance-associated proteins (MRP), but it remains unclear whether MRP proteins confer resistance to heavy metals in zebrafish. In this study, we obtained zebrafish (Danio rerio) fibroblast-like ZF4 cells with resistance to toxic heavy metals after chronic cadmium exposure and selection for 6 months. These cadmium-resistant cells (ZF4-Cd) were maintained in 5 mu M cadmium and displayed cross-resistance to cadmium, mercury, arsenite and arsenate. ZF4-Cd cells remained the resistance to heavy metals after protracted culture in cadmium-free medium. In comparison with ZF4-WT cells, ZF4-Cd cells exhibited accelerated rate of cadmium excretion, enhanced activity of MRP-like transport, elevated expression of abcc2, abcc4 and mt2 genes, and increased content of cellular GSH. Inhibition of MRP-like transport activity, GSH biosynthesis and GST activity significantly attenuated the resistance of ZF4-Cd cells to heavy metals. The results indicate that some of MRP transporters are involved in the efflux of heavy metals conjugated with cellular GSH and thus play crucial roles in heavy metal detoxification of zebrafish cells. (C) 2010 Elsevier Inc. All rights reserved.